Transdermal therapeutic system of isradipine: Effect of hydrophilic and hydrophobic matrix on In Vitro and Ex vivo characteristics

Abstract

Isradipine (ISDP) is an effective calcium channel blocker used in the treatment of hypertension. It undergoes extensive first pass metabolism and bioavailability through the oral route is only about 15 to 24%. Hence we attempted to develop a matrix type controlled transdermal drug delivery system for ISDP. Formulations A1, A2, A3 were composed of Eudragit RL100 and hydroxypropyl methyl cellulose (HPMC) in 1:3, 1:1, 3:1 ratios; A4, A5, A6 were composed of Eudragit RS100 and HPMC in 1:3, 1:1, 3:1 ratios. All six formulations carried 5 mg of ISDP/patch area, 5% v/w of D-limonene, 15 % v/w of propylene glycol in methanol:dichloromethane (1:1). The physicochemical compatibility of the drug and the polymers was studied by infrared spectroscopy and differential scanning calorimetry. The results suggested no physicochemical incompatibility between the drug and the polymers. The prepared transdermal drug delivery system were evaluated for physicochemical characteristics, mainly in vitro release and ex vivo permeation. The ex vivo permeation studies were carried out across excised rat skin using Franz diffusion cell. All the formulations exhibited satisfactory physicochemical characteristics. Cumulative amount of the drug released in 36 h from the six formulations were 1695.32, 1527.89, 1455.54, 1485.65, 1282.81 and 916.88 microg/cm(2) respectively. Corresponding values for the cumulative amounts of drug permeated across the rat skin for the above matrix films were 1456.29, 1284.70, 1182.99, 1212.72, 1046.05, and 782.60 microg/cm(2) respectively. By fitting the data into zero order, first order and Higuchi models, it was concluded that drug release from matrix films followed Higuchi model and the mechanism of drug release was diffusion mediated. Based on the physical evaluation, in vitro drug release and ex vivo permeation characteristics, it was concluded that for potential therapeutic use, monolithic drug matrix films A1, may be suitable for the development of a transdermal drug delivery system of ISDP.

Influence of the Component Excipients on the Quality and Functionality of a Transdermal Film Formulation

“…The film thickness appeared to decrease with decreasing ratio of the Methocel ® E15:Eudragit ® polymer in the formulations. These results are in agreement with those reported previously (31,32). The results of the flatness study showed that the formulation films had a negligible change in the length along the longitudinally cut edges, indicating a near 100% flatness.…”

“…The moisture content and the moisture uptake values of the prepared films were found to be dependent on the incorporated hydrophilic polymer ratio. An increase in the moisture content and moisture uptake by polymeric films as a function of increasing levels of hydrophilic polymers has been reported earlier (18,31,32,39). A small amount of moisture in the films is thought to be essential to maintain the stability and integrity of the films and to prevent excessive drying (resulting in brittleness and cracking) of the films (18,39).…”

Transdermal delivery of Diltiazem HCl from matrix film: Effect of penetration enhancers and study of antihypertensive activity in rabbit model

“…Different plasticizers such as glycerol, DBT and PG were incorporated at 20% w/w of polymer dry weight. Calculated amount of DTH was mixed with homogenous polymer solution and poured into a petri dish containing mercury [12,13]. A funnel was placed over the petri dish in inverted position to control the rate of evaporation.…”

Optimization of Biopolymer Based Transdermal Films of Metoclopramide as an Alternative Delivery Approach

“…Our results indicate that MTC release from transdermal films followed Higuchi model (r 2 = 0.98-0.99). This observation implies that the drug released from all transdermal films prepared follows matrix diffusion mechanism, in which the rate controlling step is the process of diffusion through matrix polymer base [44][45][46]. The regular release of MTC from all formulations led to prove the homogeneous physical structure of the films.…”